It is often desired to provide particles that are swellable. It is sometimes desired that such swellable particles be relatively large, and it is also sometimes desired that such swellable particle be provided in a collection that has relatively few “fines” (i.e., particles with small diameter relative to the mean particle size of the collection). One use for such swellable particles is in the production of polymeric particles, and the polymeric particles thus produced are useful for one or more of a variety of purposes. Some of such polymeric particles may be chosen or designed to be useful, for example, for one or more of the following purposes: light scattering and/or diffusion materials, surface coatings, surface matting agents, surface gloss reducers, surface texture modifiers, plastic additives, liquid crystal display spacers, standard samples, micro filters, controlled release agents, intermediates for preparation of chromatographic solid phases, adsorbents, solid phase synthesis resins, catalytic enzyme supports, milling media, dispersing media, enzyme immobilization materials, resins for affinity chromatography, or ion-exchange materials.
One method of producing particles is described by Frazza, et. al, in U.S. Pat. No. 5,147,937, which discloses gradually combining a monomer mixture with an aqueous dispersion of emulsion-polymerized polymer particles in the presence of a dispersion stabilizer and an oil-soluble initiator; the resultant particles are disclosed by Frazza, et. al. to be polymer particles. It is desired to provide a method of producing swellable particles. It is also desired to produce swellable particles in a collection that has a relatively large mean particle diameter and has relatively few fines. Additionally, it is desired to produce polymeric resin particles from such swellable particles, so that the collection of polymeric resin particles will also have a relatively large mean particle diameter and/or a relatively small amount of fines.
Further, it is desired to produce such collections of polymeric resin particles using processes that take a relatively short time to perform. Independently, it is additionally desired to produce such collections of polymeric resin particles without the need of uncommon equipment.
In some of the cases, the polymeric resin particles are functionalized. In such cases, it is sometimes desired that the functionalized polymeric resin particles have relatively high capacity for protein molecules. Independently, it is sometimes desired that the functionalized polymeric resin particles be useful for solid phase synthesis of peptides and/or oligonucleotides.
In a first aspect of the present invention, there is provided a method for making swellable particles, said method comprising mixing initial particles, at least one monomer, at least one initiator, and at least one chain-transfer agent, wherein said mixing is performed under conditions in which said monomer is capable of forming oligomer or polymer or a mixture thereof.
In a second aspect of the present invention, there is provided swellable particles made by a method comprising mixing initial particles, at least one monomer, at least one initiator, and at least one chain-transfer agent, wherein said mixing is performed under conditions in which said monomer is capable of forming oligomer or polymer or a mixture thereof.
In a third aspect of the present invention, there is provided polymeric resin particles made by a method comprising mixing at least one subsequent monomer with the swellable particles provided herein in the second aspect of the present invention and polymerizing said subsequent monomer.
In a fourth aspect of the present invention, there is provided functionalized polymeric resin particles made by a method comprising reacting the polymeric resin particles provided herein in the third aspect of the present invention with at least one reagent to chemically bind one or more functional groups to said polymeric resin particles, to convert a chemical group on said polymeric resin particles to a functional group, or a combination thereof.
In a fifth aspect of the present invention, there is provided a method for making swellable particles, said method comprising mixing initial particles, at least one monomer, at least one oil-soluble initiator, and at least one chain-transfer agent, wherein said mixing is performed under conditions in which said monomer is capable of forming oligomer or polymer or a mixture thereof.
In a sixth aspect of the present invention, there is provided a method for making secondary swellable particles, said method comprising mixing    (a) swellable initial particles,    (b) at least one monomer,    (c) at least one oil-soluble initiator, and    (d) at least one chain-transfer agent,wherein said mixing of said (a), (b), (c), and (d) is performed under conditions in which said monomer (b) is capable of forming oligomer or polymer or a mixture thereof, and wherein said swellable initial particles are made by a method comprising mixing    (d) initial particles,    (e) at least one monomer, wherein any or all of said monomer (e) may be the same as said monomer (b), different from said monomer (b), or a mixture thereof,    (f) at least one initiator, wherein any or all of said initiator (f) may be the same as said initiator (c), different from said initiator (c), or a mixture thereof, and    (g) at least one chain-transfer agent, wherein any or all of said chain-transfer agent (g) may be the same as said chain-transfer agent (d), different from said chain-transfer agent (d), or a mixture thereof,wherein said mixing of said (d), (e), (f), and (g) is performed under conditions in which said monomer (e) is capable of forming oligomer or polymer or a mixture thereof.
A “polymer,” as used herein and as defined by F W Billmeyer, JR. in Textbook of Polymer Science, second edition, 1971, is a relatively large molecule made up of the reaction products of smaller chemical repeat units. Polymers may have structures that are linear, branched, star shaped, looped, hyperbranched, crosslinked, or a combination thereof; polymers may have a single type of repeat unit (“homopolymers”) or they may have more than one type of repeat unit (“copolymers”). Copolymers may have the various types of repeat units arranged randomly, in sequence, in blocks, in other arrangements, or in any mixture or combination thereof.
“Polymerizing” herein means the reacting of monomers to form oligomer or polymer or a mixture thereof.
Polymer molecular weights can be measured by standard methods such as, for example, size exclusion chromatography or intrinsic viscosity. Generally, polymers have number-average molecular weight (Mn) of 1,000 or more. Polymers may have extremely high Mn; some polymers have Mn above 1,000,000; typical polymers have Mn of 1,000,000 or less. As used herein, “low molecular weight polymer” means a polymer that has Mn of less than 10,000; and “high molecular weight polymer” means a polymer that has Mn of 10,000 or higher. Some polymers are crosslinked, and crosslinked polymers are considered to have infinite molecular weight.
“Oligomers,” as used herein, are structures similar to polymers except that oligomers have fewer repeat units and have lower molecular weight. Normally, oligomers have 2 or more repeat units. Generally, oligomers have Mn of 400 or greater and have Mn of less than 2000.
Molecules that can react with each other to form the repeat units of an oligomer or a polymer are known herein as “monomers.” Typical monomers have molecular weight of less than 400. Among the monomers useful in the present invention are molecules, for example, that have at least one carbon-carbon double bond. Among such monomers are, for example, vinyl monomers, which are molecules that have at least one vinyl group (i.e., CH2═CR—, where R is a hydrogen, a halogen, an alkyl group, a substituted alkyl group, or another substituted or unsubstituted organic group). Some suitable vinyl monomers include, for example, styrene, substituted styrenes, dienes, ethylene, ethylene derivatives, and mixtures thereof. Ethylene derivatives include, for example, unsubstituted or substituted versions of the following: vinyl acetate, acrylonitrile, (meth)acrylic acids, (meth)acrylates, (meth)acrylamides, vinyl chloride, halogenated alkenes, and mixtures thereof. As used herein, “(meth)acrylic” means acrylic or methacrylic; “(meth)acrylate” means acrylate or methacrylate; and “(meth)acrylamide” means acrylamide or methacrylamide. In some embodiments, “substituted” monomers include, for example, monomers with more than one carbon-carbon double bond, monomers with hydroxyl groups, monomers with other functional groups, and monomers with combinations of functional groups.
In some embodiments, the monomers used do not include vinyl chloride. In some embodiments, the monomers used are all compounds with boiling point at 1 atmosphere pressure of 10° C. or higher.
A substance is said herein to be a “poor solvent for a polymer” if the amount of that polymer that will dissolve in that substance is 1% or less, by weight of polymer based on the weight of the substance. In cases where the polymer of interest is crosslinked, a test polymer can be made that is like the polymer of interest except that the test polymer lacks the functionality that creates the crosslinks; if a substance is a poor solvent for that test polymer, the substance is also considered to be a poor solvent for the polymer of interest. In some cases, a substance is used that is a poor solvent for a certain polymer, where the amount of that polymer that will dissolve in the substance is 0.2% or less; or 0.05% or less; by weight of polymer based on the weight of the substance.
When particles are contemplated to be used in the practice of the present invention, it is sometimes useful to characterize the size of the particles. When particles are spherical or nearly spherical, it is useful to characterize the size by characterizing the diameter of the particles.
When the diameters of a collection of particles have been characterized, it is often apparent that the collection has a distribution of diameters. One characteristic of such distributions is the mean particle diameter. Another characteristic of such distributions is the uniformity of the particle diameters.
It is contemplated that the appropriate technique will be chosen to characterize the diameters of particles of interest, depending on the type and form of particles to be measured. For example, if the particles of interest are dispersed in a transparent medium, light scattering may be used to characterize the diameter, or (if the particles are large enough), optical microscopy may be used. For another example, if the particles are dry, they may be characterized by passing them through a series of sieves of various sizes or by examining them with an electron microscope or with an optical microscope. It is also contemplated that particles of interest that are dispersed could be characterized by drying a sample of such particles and then characterizing that dried sample using a technique appropriate for dry particles.
One method of comparing the amount of fines in two distributions (a “first” distribution and a “second” distribution) of particles is as follows. A dispersion in a fluid is prepared of the first distribution of particles. The dispersion is allowed to stand, or is placed in a centrifuge, with conditions and duration chosen so that some but not all of the particles collect at the bottom of the container in a mass known herein as a “plug.” The plug is removed, dried, and weighed. The particles that remain in the dispersion are known to be the smallest particles and are considered “fines.” The “% plug” is the dry weight of the plug, as a percentage of the total dry weight of all particles in the original dispersion. The “% fines” is 100 minus the “% plug.” Then, a dispersion of the second distribution of particles can be assessed by the identical method. If the second distribution has a lower “% fines” than the first distribution, then it is known that the second distribution has lower amount of fines than the first distribution. This method is normally performed at 25° C.
When particles are dispersed in a fluid, the fluid may be an aqueous fluid or a non-aqueous fluid. The fluid in which particles are dispersed is called the “dispersion medium.” Aqueous fluids are defined herein as fluids that contain 50% to 100% water, by weight based on the weight of the fluid. Some aqueous fluids contain water in an amount, by weight based on the weight of the fluid, of 75% to 100%, or 90% to 100%. Non-aqueous fluids are fluids that are not aqueous fluids. When particles are dispersed in a fluid, the dispersion (i.e., the combination of dispersed particles and the fluid in which they are dispersed) may be, for example, a suspension, an emulsion, a miniemulsion, a microemulsion, a latex, or a combination thereof. A dispersion of particles that are dispersed in an aqueous fluid is known herein as an “aqueous dispersion.”
As used herein a “micrometer” is one millionth of a meter. Sometimes, in the art, the prefix “micro” is abbreviated with the Greek letter “mu,” and a micrometer is sometimes called a “micron.”
As used herein, a particle is “swellable” if there can be found a compound that is readily absorbed by the particle, such that the particle is larger after absorbing that compound. If the swellability of the particles is tested, it is contemplated that the size of the swollen particle could be measured by any particle-size test that is appropriate for that type of swollen particle.
The present invention involves a method of making swellable particles, and that method includes mixing particles (known herein as “initial particles”) with at least one monomer, at least one initiator, and at least one chain-transfer agent. Herein, this mixture of initial particles, at least one monomer, at least one initiator, and at least one chain-transfer agent, is called the “swellable particle formation mixture” (“SPFM”). In some embodiments, the swellable particle formation mixture optionally contains further ingredients in addition to initial particles, at least one monomer, at least one initiator, and at least one chain-transfer agent.
Initial particles may be any material that is in particulate form. In some embodiments, the initial particles are dispersed in a fluid. In some embodiments, the initial particles are dispersed in an aqueous fluid.
Initial particles may have any composition. In some embodiments, initial particles are organic compounds. In some embodiments, initial particles contain polymer, which may be made by any method, including, for example, bulk, solution, emulsion, dispersion, or suspension polymerization, or by variants or combinations thereof. In some embodiments, initial particles are made by a polymerization method (such as, for example, suspension or emulsion polymerization or a variant or combination thereof) that produces particles that contain polymer; in some cases, such particles are suitable for use as initial particles of the present invention.
Among embodiments in which initial particles are in the form of an aqueous dispersion, the dispersion may be, for example, a suspension, an emulsion, a miniemulsion, a microemulsion, a latex, or a combination thereof.
The initial particles can be produced by any of a wide variety of methods. If the methods of producing the initial particles involves polymerization, that polymerization may be a relatively simple, single-step operation, or the polymerization may be more complex, possibly involving multiple polymerizations. If multiple polymerizations are used, each of the various polymerizations may use the same monomer or monomers as any of the other polymerizations; or may use different monomer or monomers from any of the other polymerizations; or may use a combination of same monomer or monomers as any of the other polymerizations and different monomer or monomers from any of the other polymerizations. If multiple polymerizations are used, they may all be of the same type (for example, emulsion polymerization or suspension polymerization or dispersion polymerization); they may be different types (for example, one or more emulsion polymerizations preceding and/or following one or more suspension polymerizations); or a combination of same-type and different-type polymerizations may be used.
In some embodiments, some or all of the initial particles contain polymer that was made by suspension polymerization. Independently, in some embodiments, some or all of the initial particles contain polymer that was made by dispersion polymerization. Independently, in embodiments, some or all of the initial particles contain high molecular weight polymer.
Independently, in some embodiments, some or all of the initial particles contain polymer or oligomer or a mixture thereof that was made by a method that includes emulsion polymerization. In some of such embodiments, some or all of the polymer in the initial particles is low molecular weight polymer. Independently, in some of such embodiments, the emulsion polymerization includes the use of one or more chain transfer agents.
Independently, in some embodiments, some or all of the initial particles are swellable particles produced by the methods of the present invention. That is, it is contemplated that, in some embodiments, the method of the present invention will be performed on a first set of initial particles to produce swellable particles of the present invention (herein called “swellable initial particles”), which are then used as initial particles in a subsequent performance of the method of the present invention to produce swellable particles (herein called “secondary swellable particles”). In such embodiments, it is contemplated that any or all of the at least one monomer, the at least one chain transfer agent, and the at least one initiator used in making the secondary swellable particles may be the same as, different from, or a mixture thereof, as any or all of the at least one monomer, the at least one chain transfer agent, and the at least one initiator used in making the swellable initial particles. It is further contemplated that, in some embodiments, this process (i.e., using swellable particles as the initial particles in a performance of the method of the present invention to produce swellable particles) could be repeated as many times as desired.
In some embodiments of the present invention, initial particles are used that have mean particle diameter of 0.1 micrometer or more; or 0.2 micrometer or more; or 0.5 micrometer or more. Independently, in some embodiments of the present invention, initial particles are used that have mean particle diameter of 50 micrometers or less; or 25 micrometers or less; or 12 micrometers or less.
In the practice of the present invention, the method of making swellable particles involves mixing initial particles with ingredients that include at least one monomer. In some embodiments, at least one monomer is used that is capable of radical polymerization. In some embodiments, at least one vinyl monomer is used. Independently, in some embodiments, at least one monomer is used that has low solubility in water. In some embodiments, at least one monomer is used that has solubility in water at 25° C., by weight, based on the weight of water, of 1% or less; or 0.5% or less; or 0.2% or less; or 0.1% or less. In some embodiments, all the monomers used in making swellable particles have low solubility in water.
Some useful monomers for making swellable particles are, for example, vinyl aromatic monomers (including, for example, styrene and substituted styrenes), alkyl(meth)acrylates, substituted alkyl(meth)acrylates, and mixtures thereof. Some suitable monomers are alkyl(meth)acrylates with alkyl groups that have 2 or more carbon atoms, or 3 or more carbon atoms, or 4 or more carbon atoms. Independently, some suitable monomers are alkyl(meth)acrylates with alkyl groups that have 25 or fewer carbon atoms, or 12 or fewer carbon atoms, or 8 or fewer carbon atoms. In some embodiments, the monomers used include vinyl aromatic monomers, alkyl acrylates, and mixtures thereof. In some embodiments, the monomers used include at least one alkyl acrylate, the alkyl group of which has 4 to 8 carbon atoms. In some embodiments, the monomers used include butyl acrylate. Independently, in some embodiments, the monomers used include styrene, at least one substituted styrene, or a mixture thereof. In some embodiments, the monomers used include styrene. In some embodiments, the monomers used include a mixture of styrene and butyl acrylate.
In the practice of the present invention, the method of making swellable particles involves the use of at least one chain transfer agent. Chain transfer agents are compounds capable of participating in a chain transfer reaction during radical polymerization of monomer. Some suitable chain transfer agents are, for example, halomethanes, disulfides, thiols (also called mercaptans), and metal complexes. Also suitable as chain transfer agents are various other compounds that have at least one readily abstractable hydrogen atom. Mixtures of suitable chain transfer agents are also suitable. Suitable thiols include, for example, aryl thiols, alkyl thiols, alkyl dithiols, mercaptoalkanols, and alkyl esters of thioalkyl carboxylic acids. Some suitable thiols are, for example, benzene thiol, dodecyl mercaptans, hexanethiol, butanethiol, butyl 3-mercaptopropionate, ethyl 3-mercaptopropionate, butyl mercaptoacetate, 1,6-hexanedithiol, 4-mercapo-2-butanol, 4-mercapto-1-butanol, and 2-mercapto-ethanol. Suitable halomethanes include, for example, chloroform, tetrabromomethane, tetrachloromethane, and bromotrichloromethane. Some suitable disulfides include, for example, dialkyldisulfides (such as, for example diethyldisulfide), dialkylaryldisulfides (such as, for example, dibenzyldisulfide), and diaryldisulfides (such as, for example, diphenyldisulfide).
Mixtures of suitable chain transfer agents are also suitable.
When practicing the process of the present invention for making swellable particles, in some embodiments the amount of chain transfer agent will be, by weight based on the total weight of monomer used in the process of the present invention for making swellable particles, 2% or more; or 5% or more; or 10% or more. In some embodiments the amount of chain transfer agent will be, by weight based on the weight of monomer, 30% or less; or 25% or less.
In the practice of the present invention, the method of making swellable particles involves the use of at least one initiator. An initiator is a compound that is capable of producing at least one free radical under conditions in which that free radical can interact with monomer. Conditions that cause some initiators to produce at least one free radical include, for example, elevated temperature, exposure to photons, exposure to ionizing radiation, reactions of certain compounds (such as, for example, oxidation-reduction pairs of compounds), and combinations thereof.
Some initiators that are suitable for use in the method of the present invention of making swellable particles are water-soluble. As used herein, an initiator is “water-soluble” if it has solubility in water of greater than 1% by weight, based on the weight of water. Some suitable water-soluble initiators are, for example, persulfates, including, for example, sodium persulfate and ammonium persulfate. Some persulfate initiators generate radicals either by being heated or by being reacted with a reductant such as, for example, isoascorbic acid, sodium sulfoxylate formaldehyde, or sodium hydrogensulfite.
Other initiators that are suitable for use in the method of the present invention of making swellable particles are oil-soluble. As used herein, an initiator is “oil-soluble” if it has low solubility in water. Some suitable oil-soluble initiators, for example, have solubility in water, by weight, based on the weight of water, of 1% or less; or 0.1% or less; or 0.01% or less.
Some initiators that are suitable for use in the method of the present invention of making swellable particles are, for example, oil-soluble peroxides and oil-soluble azo compounds. Suitable oil-soluble peroxides include, for example, oil-soluble peroxyesters (also sometimes called percarboxylic esters or peroxycarboxylic esters), oil-soluble peroxydicarbonates, oil-soluble peroxides (such as, for example, oil-soluble dialkyl peroxides, oil-soluble diacyl peroxides, and oil-soluble hydroperoxides), oil-soluble peroxyketals, and oil-soluble ketone peroxides. Peroxyesters have the chemical structure
where R1 and R2 are organic groups, which may be the same as each other or different from each other. R1 and R2 may be, independently of each other, straight, branched, cyclic, or a combination thereof. In some embodiments, R1 and R2 may be, independent of each other, alkyl groups, alkenyl groups, aryl groups, substituted versions thereof, or combinations thereof. In some embodiments, R1 is an alkyl group with 4 or more carbon atoms, or an alkyl group with 6 or more carbon atoms. In some embodiments, R1 is an alkyl group with 20 or fewer carbon atoms, or an alkyl group with 10 or fewer carbon atoms. Independently, in some embodiments, R2 is an alkyl group with 1 or more carbon atoms, or an alkyl group with 3 or more carbon atoms. Independently, in some embodiments, R2 is an alkyl group with 10 or fewer carbon atoms, or an alkyl group with 6 or fewer carbon atoms. Suitable initiators include, for example, t-butyl peroctoate. Among suitable oil-soluble diacyl peroxides are, for example, aromatic diacyl peroxides (such as, for example, benzoyl peroxide) and aliphatic diacyl peroxides (such as, for example lauroyl peroxide).
Some azo compounds suitable as oil-soluble initiators are those, for example, with structure R3—N═N—R4, where R3 and R4 are, independently, unsubstituted or substituted organic groups, at least one of which contains a nitrile group. Some examples of such azo compounds are those with the structure
where R5, R6, R7, and R8 are each, independently of each other, a hydrogen or an organic group such as, for example, a methyl group, an ethyl group, an alkyl group with 3 or more carbon atoms, or a substituted version thereof. In some embodiments, R5, R6, R7, and R8 are each, independently of each other, selected from the group consisting of alkyl groups with 1 to 3 carbon atoms. Some suitable initiators include, for example, 2,2′-azobis(2-methylbutanenitrile) and 2,2′-azobis(2,4-dimethylpentanenitrile).
Mixtures of suitable initiators are also suitable.
When practicing the process of the present invention for making swellable particles, in some embodiments the amount of initiator will be, by weight based on the total weight of monomer used in the process of the present invention for making swellable particles, 0.1% or higher, or 0.2% or higher, or 0.5% or higher. In some embodiments the amount of initiator will be, by weight based on the total weight of monomer used in the process of the present invention for making swellable particles, 8% or less, or 4% or less, or 2% or less.
In some embodiments, the swellable particle formation mixture of the present invention optionally further includes one or more stabilizer. Stabilizers are water-soluble polymers such as, for example, poly(vinyl alcohol), cellulose ethers, and mixtures thereof. Suitable cellulose ethers include, for example, cellulose that has been subjected to etherification, in which some or all of the H atoms in the hydroxyl groups are replaced by alkyl groups, hydroxy alkyl groups, alkyl ether groups, or a mixture thereof. In some of the embodiments in which one or more stabilizers are used in the process of the present invention for making swellable particles, the amount of stabilizer is, by weight of stabilizer, based on the dry weight of initial particles, 1% or more; or 2% or more. Independently, in some of the embodiments in which one or more stabilizers are used in the process of the present invention for making swellable particles, the amount of stabilizer is, by weight of stabilizer, based on the dry weight of initial particles, 15% or less; or 7% or less. In some embodiments, no stabilizer is used in the process of the present invention for making swellable particles.
In the process of the present invention of making swellable particles, the mixing of the ingredients may be performed by any method, in any order, as long as the process involves, at some time, a mixture that includes (optionally, among other ingredients) initial particles, monomer, chain-transfer agent, and initiator, is present under conditions in which the monomer is capable of polymerizing. It is contemplated that, in some embodiments, the ingredients may be mixed continuously as they flow through a continuous-flow reactor. It is also contemplated that, in some embodiments, some of the ingredients may be placed in a vessel and the other ingredients may be added (together or individually; gradually or suddenly) to that vessel.
As used herein “conditions in which monomer is capable of forming oligomer or polymer or a mixture thereof” means conditions in which polymerization can proceed usefully quickly. To test if a particular set of conditions are “conditions in which monomer is capable of forming oligomer or polymer or a mixture thereof”, the conditions could be held constant, without adding or removing any ingredients, and the amount of monomer present could be measured. Under “conditions in which monomer is capable of forming oligomer or polymer or a mixture thereof,” after conditions are held constant for one hour, 5% or more of the monomer (by weight, based on the weight of monomer present at the beginning of the one hour period) will have reacted to form oligomer or polymer or a mixture thereof. In some cases, 10% or more, or 20% or more, or 50% or more of the monomer will have reacted to form oligomer or polymer or a mixture thereof.
Polymerizing in the practice the method of the present invention for making swellable particles is conducted by providing conditions in which the monomers can and do react to form at least one oligomer or polymer or mixture thereof. In some embodiments, the amount of monomer consumed in the formation of polymer is 90% or more; or 95% or more; or 99% or more, by weight of monomer consumed, based on the total weight of monomer used in the process of making swellable particles.
In some embodiments (herein called “addition to aqueous initial particle embodiments” or “AAIP embodiments”), some or all of the initial particles are in the form of an aqueous dispersion; these initial particles are placed in a vessel; and the “SPFM remaining ingredients” (i.e., all the ingredients of the swellable particle formation mixture other than the initial particles) are then added to that vessel. In AAIP embodiments, the SPFM remaining ingredients may be added individually to the vessel containing initial particles; or some or all of the SPFM remaining ingredients may be mixed together before the mixture is added to the vessel containing initial particles; or some combination of individual SPFM remaining ingredients and mixtures of SPFM remaining ingredients may be added to the vessel containing initial particles. Among AAIP embodiments in which not all the SPFM remaining ingredients are mixed together prior to adding them to the vessel, it is contemplated that, in some embodiments, any SPFM remaining ingredients that are not mixed together may be added separately and simultaneously to the vessel containing initial particles.
Independently, in some AAIP embodiments, one or more of the SPFM remaining ingredients are in the form of an aqueous dispersion prior to being added to the vessel containing initial particles. When such an aqueous dispersion is formed, any method of forming a dispersion may be used. For example, one or more SPFM remaining ingredients may be mixed with water and one or more surfactants. If the one or more SPFM remaining ingredients are liquids, the resulting dispersion is commonly called an emulsion. Such aqueous dispersions are often made by methods that include mixing the mixture of one or more SPFM remaining ingredients with one or more surfactants in the presence of mechanical agitation. In some embodiments, the mechanical agitation provides “high shear” (i.e., it imparts a high shear rate to the ingredients).
When an aqueous dispersion is formed using mechanical agitation, the mechanical agitation may be supplied by any method that results in an aqueous dispersion. Some suitable mechanical agitation methods include, for example, shaking the mixture, stirring the mixture, or passing the mixture through a static mixing element. Suitable stirring methods include, for example, contacting the mixture with a rotating device such as, for example, a magnetic bar or an impeller. One suitable arrangement of a rotating device, for example, is to fix the rotating device in a pipe or other conduit and pass the mixture continuously through the pipe or other conduit, past the rotating device. Another suitable arrangement of a rotating device, for example, is to place a fixed volume of mixture and the rotating device into a container and rotate the rotating device within the fixed volume of mixture until a dispersion is formed.
Some suitable impellers include, for example, axial flow impellers (including, for example, propellers and pitched blade turbines), radial flow impellers (including, for example, open flat blade impellers, disk style impellers, backswept open impellers, and backswept with disk impellers), hydrofoil impellers, high shear impellers (including, for example, bar turbines, sawtooth impellers, and rotor/stators), and close-clearance impellers (including, for example, anchor impellers, helical ribbons, and wall scrapers). Sometimes, the process of forming a dispersion using a high shear impeller is referred to as “homogenizing.”
In some of the embodiments in which at least one ingredient other that the initial particles is in the form of an aqueous dispersion, the dispersion of that ingredient may be stabilized with one or more dispersant or surfactant or mixture thereof. When a dispersant or surfactant is used, it is desirably chosen to be compatible with any other aqueous dispersions that are used in the practice of the present invention. Suitable surfactants include, for example, cationic surfactants, nonionic surfactants, amphoteric surfactants, and anionic surfactants. Among the suitable nonionic surfactants are, for example, alkyl ether polymers (including block polymers) and alkyl phenol polyalkyloxylates (such as, for example, alkyl phenol polyethoxylates). Among the suitable anionic surfactants are, for example, carboxylate surfactants, sulfonate surfactants, sulfate surfactants, and phosphate surfactants. Some suitable anionic surfactants are, for example, alkyl carboxylates, alkenyl carboxylates, alkylbenzene sulfonates, alkyl sulfates, and alkyl phosphates. In some embodiments, alkylbenzene sulfonates or alkyl sulfates or mixtures thereof are used. In some embodiments, alkylbenzene sulfonates are used. Mixtures of suitable surfactants are also suitable.
When an ingredient or mixture of ingredients is in the form of an aqueous emulsion, the amount of surfactant used in some embodiments, by weight of surfactant based on total weight of the ingredient or ingredients in the emulsion, is 0.05% or more; or 0.1% or more. Independently, in some embodiments the amount of surfactant used, by weight of surfactant based on total weight of the ingredient or ingredients in the emulsion, is 10% or less; or 5% or less.
In the process of the present invention for making swellable particles, the ingredients are mixed under conditions in which the monomer is capable of polymerizing. In some embodiments, such conditions are established when the conditions necessary for the initiator to form free radicals are present. For example, in such embodiments, when an initiator is used that produces free radicals when the temperature is high enough, it is contemplated that the ingredients will be mixed at a temperature high enough so that the initiator produces enough free radicals so that the monomer in the mixture is capable of polymerizing. It is further contemplated that the conditions under which mixing takes place will also provide other aspects that may be necessary for polymerization to occur, such as, for example, sufficient agitation to ensure mixing, and, for another example, transport conditions that allow free radicals and monomer molecules to react.
In some embodiments of the present invention, one or more materials may or may not be mixed with some or all of the initial particles prior to formation of the swellable particle formation mixture. For example, in embodiments in which initial particles are used in the form of a dispersion, it is useful to consider substances herein called “swellants,” which are compounds that are more compatible with the initial particles than with the dispersion medium, that have relatively low molecular weight, and that are not monomers. Some swellants have solubility in the dispersion medium of the initial particles, by weight, based the weight of the dispersion medium, of 5% or less, or 2% or less, or 1% or less. Independently, some swellants have molecular weight of 1,000 or lower; or 500 or lower. Common swellants are, for example, plasticizers, solvents, or mixtures thereof.
In some embodiments, prior to formation of the complete swellable particle formation mixture, the amount of plasticizer present in any mixture with initial particles, by weight, based on the total dry weight of initial particles, is 10% or less; or 3% or less; or 1% or less; 0.3% or less; or 0.1% or less; or none. Independently, in some embodiments, prior to formation of the complete swellable particle formation mixture, the amount of solvent present in any mixture with initial particles, by weight, based on the total dry weight of initial particles, is 10% or less; or 3% or less; or 1% or less; 0.3% or less; or 0.1% or less; or none. Independently, in some embodiments, prior to formation of the complete swellable particle formation mixture, the amount of any swellant present in any mixture with initial particles, by weight, based on the total dry weight of initial particles, is 10% or less; or 3% or less; or 1% or less; 0.3% or less; or 0.1% or less; or none.
In the practice of the method of the present invention for forming swellable particles, in some embodiments, some monomer may or may not be mixed with some or all of the initial particles prior to formation of the complete swellable particle formation mixture. In some embodiments, prior to formation of the complete swellable particle formation mixture, the amount of monomer present in any mixture with initial particles, by weight, based on the total dry weight of initial particles, is 10% or less; or 3% or less; or 1% or less; 0.3% or less; or 0.1% or less; or none.
In the practice of the method of the present invention for forming swellable particles, in some embodiments, some chain-transfer agent may or may not be mixed with some or all of the initial particles prior to formation of the complete swellable particle formation mixture. In some embodiments, prior to formation of the complete swellable particle formation mixture, the amount of chain-transfer agent present in any mixture with initial particles, by weight, based on the total dry weight of initial particles, is 10% or less; or 3% or less; or 1% or less; 0.3% or less; or 0.1% or less; or none.
In the practice of the method of the present invention for forming swellable particles, in some embodiments, it is possible to have some initiator mixed with some or all of the initial particles prior to formation of the complete swellable particle formation mixture. In other embodiments, no initiator is mixed with any of the initial particles prior to formation of the complete swellable particle formation mixture.
In the practice of the method of the present invention for forming swellable particles, in some embodiments, it is possible to have some monomer mixed with some or all of the initial particles prior to formation of the complete swellable particle formation mixture. In other embodiments, no monomer is mixed with any of the initial particles prior to formation of the complete swellable particle formation mixture.
Various methods are contemplated in the practice of the method of the present invention for forming swellable particles. In some embodiments, some or all of the initial particles are mixed with one, two, or all three of some of the monomer, some of the chain transfer agent, and some of the initiator, prior to establishing conditions in which the monomer is capable of polymerizing. In such embodiments, it is contemplated that the remaining portion (or entire portion) of each of the chain transfer agent, monomer, and initiator is mixed with the initial particles under conditions in which the monomer is capable of polymerizing. Also contemplated are embodiments in which the swellable particle formation mixture is first formed and the conditions in which the monomer is capable of polymerizing are first established when the first portion of monomer, the first portion of chain transfer agent, and the first portion of initiator are all simultaneously (and, optionally, separately) added to the initial particles.
The swellable particles of the present invention, after they are made, may or may not contain swellant. In some embodiments, the amount of swellant present in the swellable particles of the present invention is, by weight, based on the total dry weight of the swellable particles, 10% or less; or 3% or less; or 1% or less; 0.3% or less; or 0.1% or less; or none.
While the present invention is not limited to any particular mechanism, it is contemplated that, in some embodiments, while the method of the present invention for making swellable particles is being performed, some or all of at least one monomer that is mixed with initial particles follows the following steps: such monomer becomes resident on or in the initial particles, possibly causing the initial particles to swell; such monomer then encounters one or more free radicals (presumably formed from one or more initiators) that are also resident on or in the initial particles; and such monomer then participates with other such monomer or monomers in a polymerization reaction. For example, in some AAIP embodiments, at least one monomer and at least one initiator are added gradually and simultaneously (either together in a single mixture, or simultaneously but separately); in such AAIP embodiments, it is contemplated that some monomer enters the initial particles and polymerizes there, as further monomer is gradually added to the vessel. In some of such AAIP embodiments, at least one oil-soluble initiator is used.
In some embodiments of the present invention, the mean particle diameter of the swellable particles is larger than the mean particle diameter of the initial particles. In some embodiments, the mean particle diameter of the swellable particles of the present invention is larger than the mean particle diameter of the initial particles by a factor of 1.5 times or higher; or 2 times or higher; or 4 times or higher. Independently, in some embodiments, the swellable particles have mean particle diameter of 0.25 micrometer or more; or 0.5 micrometer or more; or 1 micrometer or more; or 2 micrometers or more; or 4 micrometers or more; or 8 micrometer or more. Independently, in some embodiments of the present invention, swellable particles have mean particle diameter of 100 micrometers or less; or 50 micrometers or less; or 25 micrometers or less.
In some embodiments, the swellable particles of the present invention contain oligomer or low molecular weight polymer or a mixture thereof. In some embodiments, the material formed during the method of the present invention for making swellable particles contains oligomer or low molecular weight polymer or a mixture thereof.
One advantage of the method of the present invention for making swellable particles is that the method can be performed in a reasonable duration. The duration of the method is the period from the time the SPFM is first formed until the time at which all of the intended monomer has been added and the polymerization of that monomer is at least 90% complete. By “% complete” is meant herein the weight of unreacted monomer (i.e., monomer that has not been incorporated into an oligomer or polymer molecule) based on the weight of all the monomer added during the performance of the method for making swellable particles. In some embodiments, the end of the duration of the method is marked when the polymerization of monomer is at least 95% complete, or at least 99% complete. In some embodiments, the duration of the method is 24 hours or less; or 12 hours or less; or 8 hours or less.
One use for the swellable particles of the present invention is as an ingredient in making polymeric resin particles. When the swellable particles of the present invention are used in making polymeric resin particles, the method of making such polymeric resin particles includes, among other steps, mixing the swellable particles of the present invention with at least one monomer (herein called “subsequent monomer” to distinguish it from monomer used in making the swellable particles). Each of the subsequent monomer or monomers may independently be the same as or different from any or all of the monomer or monomers used in making the swellable particles. The method of making such polymeric resin particles further includes polymerizing the at least one subsequent monomer.
Polymerizing in the practice of the method of the present invention for making polymeric resin is conducted by providing conditions in which the subsequent monomers can and do react to form at least one oligomer or polymer or mixture thereof. In some embodiments, the amount of monomer consumed in the formation of polymer is 90% or more; or 95% or more; or 99% or more, by weight of monomer consumed, based on the total weight of subsequent monomer used in the process of making polymeric resin. The subsequent monomer or monomers may be mixed with the swellable particles before the start of the polymerization, during the polymerization, or a combination thereof. In some embodiments, exactly one step of mixing swellable particles with subsequent monomer and exactly one step of polymerizing the subsequent monomer will be performed. In some embodiments, more than one of such mixing step may be performed, and, independently, in some embodiments, more than one polymerizing step may be performed. In some embodiments, after a first portion of subsequent monomer is mixed with swellable particles and polymerized, the resulting composition may be mixed with one or more further portions of subsequent monomer (each of which may independently be the same as or different from monomers included in previous portions of subsequent monomer), which would then be polymerized.
In some embodiments, the polymeric resin particles contain high molecular weight polymer or crosslinked polymer or a mixture thereof. In some embodiments, the polymer made by polymerizing the at least one subsequent monomer contains a high molecular weight polymer or a crosslinked polymer or a mixture thereof. One useful method of observing the presence of crosslinked polymer is to test the solubility of the polymer of interest; crosslinked polymers are generally not soluble in any solvent. In many samples of polymeric resin particles, the amount of polymer that is crosslinked is characterized by the portion of the polymeric resin particles that is not soluble. In some embodiments, polymeric resin particles made by polymerizing the at least one subsequent monomer contains an amount of material that is not soluble, by dry weight, based on the dry weight of polymeric resin particles, of 50% or more; or 75% or more; or 90% or more.
Some monomers suitable as subsequent monomer in the practice of the present invention include, for example, vinyl monomers. Suitable vinyl monomers include those with a single vinyl group, those with multiple vinyl groups, and mixtures thereof. Some suitable vinyl monomers include, for example, vinyl carboxylates, vinyl urethane monomers, vinyl aromatic monomers, (meth)acrylate esters, substituted (meth)acrylate esters, and mixtures thereof. One example of a vinyl carboxylate is vinyl acetate. One example of a vinyl urethane monomer is triallyl isocyanurate. Examples of suitable vinyl aromatic monomers include styrene, divinyl benzene, and substituted versions thereof (such as, for example, alpha-methyl styrene). Some suitable substituted (meth)acrylate esters include, for example, esters of polyhydric alcohols with (meth)acrylic acid, such as, for example, ethylene glycol dimethacrylate, glycerol dimethacrylate, and mixtures thereof.
Further examples of vinyl monomers suitable as subsequent monomers are alkyl esters of (meth)acrylic acid where the alkyl group has a functional group. In some cases, such a functional group is capable of reacting with other groups (which may be the same as or different from the functional group), either during or after polymerization of the subsequent monomer. In some of such cases, the reacting of the functional group with other groups creates branch points or crosslink junctions in the polymer that results from polymerizing the subsequent monomer. One example of such a functional group is the glycidyl group. One example of this type of monomer is glycidyl methacrylate.
Mixtures of monomers suitable as subsequent monomers are also suitable as subsequent monomers.
In some embodiments, polymeric resin particles have mean particle diameter of 1 micrometer or more; or 3 micrometer or more; or 10 micrometer or more. Independently, in some embodiments of the present invention, polymeric resin particles have mean particle diameter of 1000 micrometers or less; or 600 micrometers or less; or 250 micrometers or less; or 100 micrometers or less.
In some embodiments of the method of the present invention for making polymeric resin particles, no chain transfer agent is used beyond whatever chain transfer agent was used in the formation of the swellable particles.
When the swellable particles of the present invention are present as an aqueous dispersion, some embodiments of the method of the present invention of making polymeric resin particles involve mixing subsequent monomer with the aqueous dispersion and polymerizing the subsequent monomer in the mixture so formed. Such embodiments are known herein as “DSP” embodiments.
In some DSP embodiments, polymerizing of subsequent monomer may be performed using, for example, emulsion polymerization, suspension polymerization, dispersion polymerization, or a combination thereof. Independently, in some DSP embodiments, one or more subsequent monomers is formed into an aqueous emulsion, which is then added to the aqueous dispersion of swellable particles.
In some DSP embodiments, various optional ingredients may or may not be included in the mixture of aqueous dispersion of swellable particles and subsequent monomer. Such optional ingredients may be added, for example, to aid in conducting the polymerizing of subsequent monomer or to affect the properties of the finished polymeric resin particles. Such optional ingredients may be added before, during, or after the mixing of aqueous dispersion of swellable particles with subsequent monomer. Optional ingredients include, for example, one or more of initiators, stabilizers, porogens, other compounds, and mixtures thereof.
When one or more initiators are used in a DSP embodiment, the same initiator or initiators are suitable for polymerizing subsequent monomer as the initiators described herein above as suitable for use in the process of the present invention for making swellable particles. When one or more initiators are used in a DSP embodiment, each of the initiator or initiators used may independently be the same or different from any of the initiator or initiators used in making the swellable particles.
When practicing the process of the present invention for making polymeric resin particles, in some embodiments the amount of initiator will be, by weight based on the total weight of subsequent monomer used, 0.1% or higher, or 0.2% or higher, or 0.5% or higher. In some embodiments the amount of initiator will be, by weight based on the total weight of subsequent monomer used, 8% or less, or 4% or less, or 2% or less.
Some DSP embodiments involve the use of one or more stabilizers, while some DSP embodiments do not involve the use of stabilizers. Compounds described herein above as suitable as stabilizers in the method of the present invention for making swellable particles are also suitable as stabilizers in the method of the present invention for making polymeric resin particles. Among those embodiments in which a swellable particle that was made using one or more stabilizers is used in making polymeric resin particles that are made using a method that includes the use of one or more stabilizers, any of the stabilizers used in making the polymeric resin particles may independently be the same as or different from any of the stabilizers that were used in making the swellable particles. When one or more stabilizers are used in making polymeric resin particles, in some embodiments the amount of stabilizer, by weight based on the dry weight of swellable particles, is 1% or more; or 2% or more; or 4% or more. When one or more stabilizers are used in making polymeric resin particles, in some embodiments the amount of stabilizer, by weight based on the dry weight of polymeric resin particles, is 50% or less; or 30% or less.
Some DSP embodiments involve the use of one or more porogens. Porogens are compounds that are not monomers; that are more soluble in one or more subsequent monomer than in water; and that are poor solvents for the polymer formed by polymerizing the subsequent monomer or monomers. Some suitable porogens are, for example, hydrocarbons, alcohols, ethers, ketones, and esters. The hydrocarbon portion of suitable porogen molecules may be linear, branched, cyclic, or a combination thereof. Some suitable hydrocarbon porogens are aliphatic hydrocarbons such as, for example, iso-octane. Further suitable hydrocarbon porogens are aromatic-containing hydrocarbons such as, for example, xylene or toluene. Some suitable ester porogens are, for example, esters of aromatic carboxylic acids, such as, for example, dialkyl phthalates. Further suitable ester porogens are, for example, esters of aliphatic carboxylic acids, such as, for example, butyl acetate. Some suitable ether porogens include, for example, dialkyl ether porogens with alkyl groups having 3 or more carbon atoms, such as, for example, dibutyl ether. Some suitable alcohol porogens are, for example, alcohols of linear, branched, or cyclic alkyls with 5 or more carbon atoms, including, for example, cyclohexanol or 4-methyl-2-pentanol. Some suitable ketone porogens are, for example, dialkyl ketones such as, for example, methyl isobutyl ketone. Mixtures of suitable porogens are also suitable.
In some embodiments of the process of the present invention for making polymeric resin particles, the ratio of the weight of porogen to the total weight of all subsequent monomer is 0.1 or higher; or 0.25 or higher; or 0.5 or higher. In some embodiments of the process of the present invention for making polymeric resin particles, the ratio of the weight of porogen to the total weight of all subsequent monomer is 10 or lower; or 5 or lower; or 2.5 or lower.
In the process of the present invention for making polymeric resin particles, in some embodiments, one or more ingredients (either one or more subsequent monomer or one or more optional ingredients or a combination thereof) may be used in the form of an aqueous emulsion.
When one or more ingredients in the method of the present invention for making polymeric resin particles is in the form of an emulsion, the suitable dispersants and surfactants (and their amounts) are the same as those discussed herein above as suitable for use in emulsion of ingredients used in the method of the present invention for making swellable particles. Any dispersant or surfactant used in the method of the present invention for making polymeric resin particles may independently be the same as or different from any dispersant or surfactant that was used in making the swellable particles. If more than one ingredient in the making of the polymeric resin particles is in the form of an emulsion, the ingredients may be mixed together in a single emulsion, or they may be in different emulsions, or any combination thereof. If more than one emulsion of ingredients is used in the method of the present invention for making polymeric resin particles, the dispersants or surfactants may be the same or different or any combination thereof in the emulsions. Suitable anionic surfactants include, for example, sulfonate surfactants such as, for example, dialkyl sulfosuccinate surfactants.
The polymeric resin particles of the present invention may be used with or without being functionalized. “Functionalized” herein means that the polymeric resin particles are reacted with at least one reagent to chemically bind one or more functional groups (such as, for example, ions) to the polymeric resin particles or to convert a chemical group on the polymeric resin particle (such as, for example, an ester group) to a functional group (such as, for example, a carboxyl group). Functionalized polymeric resin particles are often useful as ion-exchange resins. Polymeric resin particles of the present invention may be functionalized to form, for example, strong cation exchange resins, strong anion exchange resins, weak cation exchange resins, weak anion exchange resins, other functionalized resins, and combinations and mixtures thereof. In some embodiments, polymeric resin particles of the present invention are formed into strong cation exchange resins by reacting the polymeric resin particles with one or more sulfonating agent (such as, for example, sodium dithionite or sodium sulfite). In some embodiments, polymeric resin particles of the present invention are formed into strong anion exchange resins by reacting the resins with one or more amine compound, such as, for example, trimethylammonium chloride. In some embodiments, polymeric resin particles of the present invention are formed into weak anion exchange resins by reacting the polymeric resin particles with one or more amine compound, such as, for example, diethylamine hydrochloride. In some embodiments, polymeric resin particles of the present invention are formed into weak cation exchange resins by, for example, reacting the polymeric resin particles with sodium hydroxide to hydrolyze ester groups on the polymeric resin particles to carboxyl groups.
Some functionalized polymeric resin particles of the present invention have good capacity and recovery when used with proteins, as measured, for example, using the methods described herein in Example 35. Independently, some functionalized resin particles of the present invention have good performance when salt, such as, for example, sodium chloride is present; that is, such resin particles have good capacity and recovery when used with proteins in the presence of relatively high levels of salt. Examples of measurements of capacity and recovery in the presence of salt are described herein in Example 35.
Independently, some functionalized polymeric resin particles of the present invention have good rigidity, as measured, for example, by the method described herein in Example 42.
Some of the polymeric resin particles of the present invention are useful for purifying biomolecules (such as, for example, proteins, enzymes, and other biomolecules). Such purifying is sometimes performed by contacting the polymeric resin particles with an aqueous solution of mixed biomolecules, for example by placing the polymeric resin particles in a liquid chromatography column and passing the aqueous solution through the column.
Some of the functionalized polymeric resin particles of the present invention are useful for purifying biomolecules (such as, for example, proteins, enzymes, and other biomolecules). Such purifying is sometimes performed by contacting the functionalized polymeric resin particles with an aqueous solution of mixed biomolecules, for example by placing the functionalized polymeric resin particles in a liquid chromatography column and passing the aqueous solution through the column.
An advantage to some of the methods of the present invention is that they can be conducted at reasonable levels of productivity. That is, in some embodiments, the methods of the present invention use commercially useful methods of polymerization (such as, for example, emulsion, suspension, and dispersion polymerization, and combinations thereof), and the practitioner of the methods of the present invention can produce swellable particles or polymeric resin particles or both, with resulting levels of productivity that are normal for such commercially useful processes. For example, the methods of the present invention can be practiced on a large scale. That is, a relatively large vessel could be used to produce a relatively large batch of material. It is contemplated that in some embodiments, a batch of swellable particles could be made that is 10 liters or larger; or 100 liters or larger; or 1,000 liters or larger. Independently, it is contemplated that in some embodiments, a batch of polymeric resin particles could be made that is 10 liters or larger; or 100 liters or larger; or 1,000 liters or larger. Independently, it is contemplated that in some embodiments, a batch of swellable particles could be made that has 3 kg or more of swellable particles by dry weight; or 30 kg or more; or 300 kg or more. Independently, it is contemplated that in some embodiments, a batch of polymeric resin particles could be made that has 5 kg or more of swellable particles by dry weight; or 50 kg or more; or 500 kg or more.
Independently, an advantage to some of the methods of the present invention is that they can be performed using normal commercial equipment for polymerization. In some embodiments, the methods of the present invention may be performed without the use of unusual equipment such as, for example, jets or frits.
Another independent advantage of some of the methods of the present invention for making polymeric resin particles is that these methods can be performed in a reasonable duration. The duration of the method is the period from the time any subsequent monomer is mixed with any swellable particles until the time at which all of the intended subsequent monomer has been added and the polymerization of that monomer is at least 90% complete. By “% complete” is meant herein the weight of unreacted monomer (i.e., monomer that has not been incorporated into an oligomer or polymer molecule) based on the weight of all the monomer added during the performance of the method for making swellable particles. In some embodiments, the end of the duration of the method is marked when the polymerization of subsequent monomer is at least 95% complete, or at least 99% complete. In some embodiments, the duration of the method for making polymeric resin particles is 48 hours or less; or 36 hours or less; or 24 hours or less; or 18 hours or less.
In some embodiments of the method of the present invention for making polymeric resin particles, swellable particles of the present invention are mixed with subsequent monomer, a period of time (known herein as the “swell time”) is allowed to elapse before polymerization takes place, and then the conditions in which the subsequent monomer polymerizes are established. In some of such embodiments, the swell time is 12 hours or less, or 10 hours or less, or 8 hours or less, 6 hours or less, or 2 hours or less.
It is considered an advantage of some of the methods of the present invention for making polymeric resins that swell times are generally lower in the method of the present invention than swell times of previously known methods for making polymeric resins. This advantage is especially observed when resins of the present invention are compared with resins made by previously known methods using similar monomers, and when the ratio of seed to final resin in the previously known method is similar to the ratio of swellable particle to final resin in the method of the present invention.